Efferent limb stimulation prior to loop ileostomy closure: a systematic review and meta-analysis.

BACKGROUND: Postoperative ileus (POI) remains a common phenomenon following loop ileostomy closure. Our aim was to determine whether preoperative physiological stimulation (PPS) of the efferent limb reduced POI incidence. METHODS: A PRISMA-compliant meta-analysis searching PubMed, EMBASE and CENTRAL databases was performed. The last search was carried out on 30 January 2023. All randomized studies comparing PPS versus no stimulation were included. The primary endpoint was POI incidence. Secondary endpoints included the time to first passage of flatus/stool, time to resume oral diet, need for nasogastric tube (NGT) placement postoperatively, length of stay (LOS) and other complications. Random effects models were used to calculate pooled effect size estimates. Trial sequential analyses (TSA) were also performed. RESULTS: Three randomized studies capturing 235 patients (116 PPS, 119 no stimulation) were included. On random effects analysis, PPS was associated with a quicker time to resume oral diet (MD - 1.47 days, 95% CI - 2.75 to - 0.19, p = 0.02), shorter LOS (MD - 1.47 days, 95% CI - 2.47 to - 0.46, p = 0.004) (MD - 1.41 days, 95% CI - 2.32 to - 0.50, p = 0.002, I2 = 56%) and fewer other complications (OR 0.42, 95% CI 0.18 to 1.01, p = 0.05). However, there was no difference in POI incidence (OR 0.35, 95% CI 0.10 to 1.21, p = 0.10), the requirement for NGT placement (OR 0.50, 95% CI 0.21 to 1.20, p = 0.12) or time to first passage of flatus/stool (MD - 0.60 days, 95% CI - 1.95 to 0.76, p = 0.39). TSA revealed imprecise estimates for all outcomes (except LOS) and further studies are warranted to meet the required information threshold. CONCLUSIONS: PPS prior to stoma closure may reduce LOS and postoperative complications albeit without a demonstrable beneficial effect on POI. Further high-powered studies are required to confirm or refute these findings.

Exploring the burden of X-linked hypophosphatemia: a European multi-country qualitative study.

INTRODUCTION: X-linked hypophosphatemia (XLH) is a rare, lifelong, progressive disease characterised by renal phosphate wasting and abnormal bone mineralisation. Symptoms begin in early childhood, with the development of rickets and related skeletal deformities and reduced growth, progressing to long-term complications, including pseudofractures and fractures, as well as pain, stiffness and fatigue. The present study was designed to explore the patient experience of pain, stiffness and fatigue and the psychosocial impact of XLH in detail. METHODS: A cross-sectional qualitative study was conducted in the United Kingdom (18), Finland (6), France (4), Germany (1) and Luxembourg (1) with XLH patients aged 26 and over. Interview discussion guides were developed in consultation with clinical experts and patient associations. Data were analysed thematically. RESULTS: Participants (N = 30) described pain, stiffness and fatigue as frequently experienced symptoms with a significant impact on physical functioning and activities of daily living (ADLs). Some also described the symptoms as impacting their mood/mental health, relationships, social life and leisure activities. Participants described how common symptoms could interact or aggravate other symptoms. Symptoms had often worsened over time, and for many, were associated with concern about the future. Most participants were worried or felt guilty about having children with XLH. The findings confirmed and extended the existing model of the burden of XLH. CONCLUSION: The present study is the first to provide an in-depth analysis of pain, stiffness and fatigue, their impact and the interrelatedness of these symptoms among adults with XLH. The study also described the psychosocial impact of XLH as a hereditary, lifelong progressive disease.

Addressing the pitfalls when designing intervention studies to discover and validate biomarkers of habitual dietary intake.

INTRODUCTION: Dietary exposure monitoring within populations is reliant on self-reported measures such as Food Frequency Questionnaires and diet diaries. These methods often contain inaccurate information due to participant misreporting, non-compliance and bias. Urinary metabolites derived from individual foods could provide additional objective indicators of dietary exposure. For biomarker approaches to have utility it is essential that they cover a wide-range of commonly consumed foods and the methodology works in a real-world environment. OBJECTIVES: To test that the methodology works in a real-world environment and to consider the impact of the major sources of likely variance; particularly complex meals, different food formulations, processing and cooking methods, as well as the dynamics of biomarker duration in the body. METHODS: We designed and tested a dietary exposure biomarker discovery and validation strategy based on a food intervention study involving free-living individuals preparing meals and collecting urine samples at home. Two experimental periods were built around three consecutive day menu plans where all foods and drinks were provided (n = 15 and n = 36). RESULTS: The experimental design was validated by confirming known consumption biomarkers in urinary samples after the first menu plan. We tested biomarker performance with different food formulations and processing methods involving meat, wholegrain, fruits and vegetables. CONCLUSION: It was demonstrated that spot urine samples, together with robust dietary biomarkers, despite major sources of variance, could be used successfully for dietary exposure monitoring in large epidemiological studies.

Estimating utilities/disutilities for high-risk metastatic hormone-sensitive prostate cancer (mHSPC) and treatment-related adverse events.

PURPOSE: To capture UK societal health utility values for high-risk metastatic hormone-sensitive prostate cancer (mHSPC) and the disutility associated with treatment-related adverse events (AEs) to inform future cost-utility analyses. METHODS: A literature review, and patient and clinical expert interviews informed the development of health states characterising mHSPC symptoms and the impact of treatment-related AEs on health-related quality of life (HRQL). Three base health states were developed describing a typical patient with high-risk mHSPC: receiving androgen deprivation therapy (ADT) [Base State 1]; receiving docetaxel plus ADT [Base State 2]; completed docetaxel and still receiving ADT whose disease has not yet progressed [Base State 3]. Six additional health states described treatment-related AEs. The health states were validated with experts and piloted with general public participants. Health state utilities were obtained using the time trade-off (TTO) method with 200 members of the UK general population. A generalised estimating equation (GEE) model was used to estimate disutility weights. RESULTS: Mean TTO scores for Base State 1 to 3 were 0.71 (SD = 0.26), 0.64 (SD = 0.27), and 0.68 (SD = 0.26), respectively, indicating that receiving docetaxel plus ADT was most impactful on HRQL. The GEE model indicated when compared to Base State 2 that the nausea and vomiting AE had the most impact on HRQL (- 0.21), while alopecia was least burdensome (- 0.04). CONCLUSIONS: The study highlights the differences in utility between base health states and the significant impact of treatment-related AEs on the HRQL of patients with mHSPC. These findings underline the importance of accounting for impaired HRQL when assessing treatments for mHSPC.

Subcortical volumetric abnormalities in bipolar disorder.

Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case-control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen's d=-0.232; P=3.50 × 10-7) and thalamus (d=-0.148; P=4.27 × 10-3) and enlarged lateral ventricles (d=-0.260; P=3.93 × 10-5) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons.

Do we have the right PROMs for measuring outcomes in lumbar spinal surgery?

PURPOSE: Patient-reported outcome measures (PROMs) have become an important part of routine auditing of outcomes in spinal surgery in the UK. PROMs can be used to help assess the quality of care provided by surgical units by determining the comparative health status of patients, before and after surgery. This study was designed to review the PROMs used to assess outcomes in spinal surgery and to determine if they are fit for the purpose. METHODS: A systematic literature search was undertaken to identify studies that reported PROMs data following lumbar spinal surgery. The PROMs that were used in each study were recorded and a separate search was undertaken to determine the evidence regarding the validity of each measure. RESULTS: The initial search identified 1142 abstracts, which were reduced through de-duplication, filtering and review to 58 articles, which were retrieved and reviewed in full. The search identified that the majority of studies used either the Oswestry Disability Index (ODI), SF-36, Roland-Morris Disability Questionnaire (RMDQ) and EQ-5D along with visual analogue scales or numeric rating scales for back and leg pain. CONCLUSIONS: The consistent use of PROMs supports the comparison of outcomes from different studies, although there was minimal evidence regarding the specificity and sensitivity of these measures for use with lumbar spinal patients. Our review highlights the need to determine a consensus regarding the use and reporting of outcome measures within the lumbar spine literature.

Neurocognitive intra-individual variability in mood disorders: effects on attentional response time distributions.

BACKGROUND: Attentional impairment is a core cognitive feature of major depressive disorder (MDD) and bipolar disorder (BD). However, little is known of the characteristics of response time (RT) distributions from attentional tasks. This is crucial to furthering our understanding of the profile and extent of cognitive intra-individual variability (IIV) in mood disorders. METHOD: A computerized sustained attention task was administered to 138 healthy controls and 158 patients with a mood disorder: 86 euthymic BD, 33 depressed BD and 39 medication-free MDD patients. Measures of IIV, including individual standard deviation (iSD) and coefficient of variation (CoV), were derived for each participant. Ex-Gaussian (and Vincentile) analyses were used to characterize the RT distributions into three components: mu and sigma (mean and standard deviation of the Gaussian portion of the distribution) and tau (the 'slow tail' of the distribution). RESULTS: Compared with healthy controls, iSD was increased significantly in all patient samples. Due to minimal changes in average RT, CoV was only increased significantly in BD depressed patients. Ex-Gaussian modelling indicated a significant increase in tau in euthymic BD [Cohen's d = 0.39, 95% confidence interval (CI) 0.09-0.69, p = 0.011], and both sigma (d = 0.57, 95% CI 0.07-1.05, p = 0.025) and tau (d = 1.14, 95% CI 0.60-1.64, p < 0.0001) in depressed BD. The mu parameter did not differ from controls. CONCLUSIONS: Increased cognitive variability may be a core feature of mood disorders. This is the first demonstration of differences in attentional RT distribution parameters between MDD and BD, and BD depression and euthymia. These data highlight the utility of applying measures of IIV to characterize neurocognitive variability and the great potential for future application.

Patients' experiences following breast cancer treatment: an exploratory survey of personal and work experiences of breast cancer patients from three European countries.

Improved treatments for early breast cancer have led to a significant increase in overall survival. While evidence regarding potential long-term sequelae of adjuvant treatments exists, relatively little research reports patients' own perceptions of change before and after adjuvant chemotherapy (AC). This study aimed to identify key ongoing issues associated with AC in daily life. An online survey developed for this study was completed by 198 women (mean age 49.7 years) in the UK, France and Germany who had AC 1-5 years previously for oestrogen receptor positive, HER2 negative early breast cancer. Women without AC and endocrine therapy, those treated with Trastuzumab or who had recurrent disease were excluded. A third of women who responded were currently unable to perform their former family role. The majority had needed support, particularly with child care, during treatment. While 54% were in full-time employment before diagnosis this had reduced to 32% following AC. Of those women still working, over half reported difficulties with tiredness or concentration. Most (85.8%) were satisfied with healthcare professionals' treatment information, but only 29.7% received information about returning to work. This exploratory survey highlights areas of women's lives affected 1-5 years following AC for early breast cancer. The impact on returning to work and issues surrounding childcare particularly, require further study.

Impact of the treatment-free interval on health-related quality of life in patients with multiple myeloma: a UK cross-sectional survey.

BACKGROUND: While the impact of various treatments on myeloma patients' health-related quality of life (HRQL) has been reported, the impact of a treatment-free interval (TFI) is currently unclear. The aims of this study were to assess if (1) a TFI is associated with a better HRQL vs. other treatment phases and (2) the length of the TFI influences HRQL. METHODS: A cross-sectional postal survey was conducted in the UK. The survey was sent to 605 multiple myeloma patients via the charity Myeloma UK and asked patients to rate their HRQL using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30), EORTC QLQ-MY20 and the EQ-5D. The results were analysed using ordinary least squares regression. RESULTS: Surveys of 402 (67 %) were returned; 370 (61 %) were considered eligible for analysis. Results demonstrated that being in a first TFI relative to other treatment phases and experiencing a longer TFI were significantly associated with better HRQL as assessed by various domains of the QLQ-C30, MY20 and EQ-5D. CONCLUSION: Patients enjoy better HRQL when in their first TFI, and the length of the TFI also positively impacts on HRQL This information may be important for patients and their physicians making treatment decisions and has implications for treatment protocols incorporating extended therapy.

Acute complicated appendicitis caused by an ingested toothpick - A case report.

INTRODUCTION AND IMPORTANCE: Acute appendicitis is one of the most common presentations to the emergency department, particularly in young adults. A combination of clinical suspicion, inflammatory blood markers and imaging modalities such as ultrasound and CT are used for its definitive diagnosis. Early detection and intervention are paramount to reduce morbidity and mortality. Laparoscopic appendicectomy is the current gold standard in the management of appendicitis, especially if complicated according to EAES guidelines. There are few documented cases in the literature of acute appendicitis secondary to foreign body ingestion. On account of this, there are currently no guidelines for its management. Our literature review highlights the importance of surgical management of foreign body acute appendicitis. CASE PRESENTATION: This case report describes the rare presentation of acute complicated appendicitis caused by an ingested toothpick in a 64 year old woman. The patient was admitted with a 3 day history of lower abdominal pain, localizing to the right iliac fossa with raised inflammatory markers. CT imaging reported acute complicated appendicitis. Laparoscopic appendicectomy was performed during which a toothpick was seen protruding through the appendiceal wall. Post operatively the patient was treated with IV antibiotics for 5 days prior to discharge. CLINICAL DISCUSSION: Due to the rare nature of foreign body appendicitis there are no specific guidelines on the respective surgical approach. A literature review showed that in the setting of foreign body appendicitis, surgical intervention is paramount with no scope for conservative management. CONCLUSION: Surgical approach is based on the clinical judgement and skillset of the operating surgeon.

Can the functional assessment of multiple sclerosis adapt to changing needs? A psychometric validation in patients with clinically isolated syndrome and early relapsing-remitting multiple sclerosis.

BACKGROUND: The Functional Assessment of Multiple Sclerosis (FAMS) is widely used in clinical trial programmes; however, it was developed before the rise in trials targeted at early stage multiple sclerosis (MS) and clinically isolated syndrome (CIS). OBJECTIVE: The aim of this study was to assess the psychometric properties of the FAMS within two clinically distinct populations, CIS and early relapsing-remitting MS (RRMS), and discern the appropriateness of the FAMS within these populations. METHODS: Secondary analysis was conducted on FAMS data from two clinical trials assessing interferon beta-1b in early RRMS and CIS. The statistical analysis assessed the scale acceptability, reliability, validity and responsiveness of the FAMS. Item response theory (IRT) was also conducted on the early RRMS sample in order to assess how well the FAMS discriminated amongst individuals with less severe MS. RESULTS: Results from both trials demonstrated an improvement in the FAMS psychometric properties with increased baseline disease severity. However, high ceiling effects were evident amongst less severe patients, and there was an overall lack of responsiveness to improvement and poor construct validity. IRT also demonstrated its lack of discrimination/sensitivity in early RRMS. CONCLUSIONS: In trials involving patients with early stage RRMS and CIS, modifications to the FAMS based on a qualitative assessment of its content validity in these populations would be required in order to potentially improve the FAMS psychometric properties and sensitivity.

Validation of a novel patient reported tool to assess the impact of treatment in erythropoietic protoporphyria: the EPP-QoL.

BACKGROUND: A novel treatment has been developed for erythropoietic protoporphyria (EPP) (a rare condition that leaves patients highly sensitive to light). To fully understand the burden of EPP and the benefit of treatment, a novel patient reported outcome (PRO) measure was developed called the EPP-QoL. This report describes work to support the validation of this measure. METHODS: Secondary analysis of trial data was undertaken. These analyses explored the underlying factor structure of the measure. This supported the deletion of some items. Further work then explored the reliability of these factors, their construct validity and estimates of meaningful change. RESULTS: The factor analyses indicated that the items could be summarised in terms of two factors. One of these was labelled EPP Symptoms and the other EPP Wellbeing, based on the items included in the domain. EPP Symptoms had evidence to support its reliability and validity. EPP Wellbeing had poor psychometric properties. CONCLUSIONS: Based on the analysis it was recommended to drop the EPP Wellbeing domain (and associated items). EPP Symptoms, despite limitations in the development of items, showed evidence of validity. This work is consistent with the recommendations of a task force that provided recommendations regarding the development, modification and use of PROs in rare diseases.

White matter lesions in euthymic patients with bipolar disorder.

OBJECTIVE: We aimed to quantify both load and regional distributions of hyperintensities on magnetic resonance imaging (MRI) in prospectively verified euthymic bipolar patients and matched controls. METHOD: Cerebral hyperintensities on T2, proton density and fluid-attenuated inversion recovery (FLAIR) MRI were compared between 48 bipolar and 47 control subjects using semi-quantitative rating scales. RESULTS: Bipolar subjects had more severe frontal deep white matter lesions (DWML). Hyperintensity load was independent of age in bipolar patients but increased with age in controls. Global prevalence and severity of hyperintensities did not differ between groups. Exploratory analysis showed DWML in excess in the left hemisphere in bipolar subjects but not in controls. CONCLUSION: Findings are consistent with clinical, particularly some neurocognitive, features of bipolar disorder and implicate fronto-subcortical circuits in its neurobiology. They more probably reflect a trait abnormality or illness scar rather than a mood state-dependent finding. Processes other than ageing and vascular factors may underlie their development.

Utilities for treatment-related adverse events in type 2 diabetes.

OBJECTIVES: The impact of Type 2 diabetes mellitus (T2DM) on health-related quality-of-life (HRQoL) is complex due to the burden of disease, lifelong treatment requirements, and comorbidities. This study aimed to capture UK societal utility values for health states associated with T2DM and treatment-related adverse events (AEs) to assess the burden of the disease and common AEs. METHODS: Nine health state descriptions were developed (from a literature review and patient and clinician qualitative input) depicting the burden associated with T2DM and treatment-related AEs. These were mild/moderate urinary tract infection (UTI); severe UTI; mycotic infection; moderate hypoglycemic events; severe hypoglycemic events; fear of hypoglycemia; gastrointestinal symptoms; and hypovolemic events. Members of the UK general public (n = 100) valued these states using the time trade-off (TTO) methodology to elicit utility values (between 0 = dead, 1 = full health). Regression analysis was conducted to understand the influence of age and gender. RESULTS: All treatment-related AEs were found to have a significant effect on utility. From the T2DM baseline state (0.92), the experience of AEs was associated with the following disutility: T2DM with hypovolemic events (0.08); T2DM with mild/moderate UTIs (0.09); T2DM with moderate hypoglycemic events (0.11); T2DM with severe hypoglycemic events (0.15); T2DM with fear of hypoglycemia (0.15); T2DM with severe UTIs (0.19); T2DM with GI symptoms (0.24); and T2DM with mycotic infection (0.25); Males consistently scored the states with significantly lower utility values, but no significant age effects emerged. CONCLUSIONS: Findings suggest that adverse events in T2DM can be a burden for some individuals. The study indicates the potential importance of including information regarding AEs in economic evaluations. Although some states were rated severely in terms of utility; in reality, many of these only last a few days, therefore having a minimal quality-adjusted life year (QALY) impact.

Dementia with Lewy bodies and AD are not associated with occipital lobe atrophy on MRI.

Dementia with Lewy bodies (DLB) is associated with occipital changes in blood flow and metabolism, but structural changes in this region have not previously been assessed. The authors performed volumetric MRI measurement of the occipital lobe blind to the diagnosis in 23 subjects with DLB, 25 with AD, and 24 age-matched control subjects. There were no significant differences between groups in occipital lobe volume. The authors conclude gross structural changes in the occipital lobe do not occur in patients with mild to moderate DLB or AD.

Comprehension of prosody in Parkinson's disease.

The evidence for a receptive prosodic loss in Parkinson's disease (PD) has remained inconclusive since the first reports in the early 1980s (Scott, Caird and Williams, 1984). The present study examined three aspects of comprehension in 11 PD patients and a group of age matched controls. Experiment 1 found no evidence of deficits in phonological discrimination or lexical access in the PD patients. Experiment 2 found that one patient (EA) was significantly impaired on a test of lexical stress discrimination. Experiment 3 examined the discrimination, comprehension and identification of utterance prosody. This experiment found that overall the PD patients were significantly impaired at the identification of utterance prosody. Patient TB was significantly worse than controls on the identification and comprehension of utterance prosody. The study has shown that PD patients can exhibit impairments in the comprehension of prosody and lexical stress. The evidence suggests that only some patients are impaired and the pattern of deficits can differ significantly.

Conditions associated with normal levels of prostate-specific antigen and elevation of prostatic acid phosphatase.

Thirteen cases are reported with normal levels of prostate-specific antigen and elevated prostatic acid phosphatase (PAP). Conditions that were associated with an elevated PAP were myeloproliferative syndromes (four cases), metastatic nonprostatic carcinoma (six cases), prostatic carcinoma (one case), tuberculosis with a concurrent lupus-like syndrome (one case), and osteomyelitis (one case). The inclusion of PAP in the initial investigation of cases with suspected prostatic disease results in a decreased specificity.

The extent of patients' understanding of the risk of treatments.

The scientific understanding of how people perceive and code risks and then use this information in decision making has progressed greatly in the last 20 years. There is considerable evidence that people employ simplifying heuristics in judgement and decision making. These heuristics may lead to bias in how people interpret information. However, much of our understanding of risk perception is based on laboratory studies. It is much less clear whether risk perception in the real world (as in the case of medical treatments) exhibits the same patterns and biases. This paper reviews the published literature on risk perception in patients who face substantial treatment risks. It examines how accurate patients' perception of risk is, what factors affect the perception of risk, and several possible explanations for why patients' risk perception is not always accurate.